There has been long recognized a desire to automate the analysis of a wide variety of substances including chemical and biochemical materials, contaminants, biological warfare agents, and generally any substance, the presence and/or amount of which is desired to be determined. In recent years, on-chip systems have been developed for molecular diagnostics, e.g., for the detection of antigens by combination with antibodies or the analysis of nucleic acids via hybridization. The systems require the mixing of conjugate antibodies or the use of fluorescent antibodies or hybridizing fluorescent molecules during preparation, and, while being miniaturized nevertheless still require macroscopic techniques such as external light sources, external electro-optical detectors, and electronic instrumentation, all of which significantly limit the size and flexibility of such on-chip devices. Particularly as would be applied to military operations there is a need for fully integrated, field portable, and sensitive chip technology which can work reliably in demanding situations. Simply scaling down existing technologies, such as fluorescent measurement schemes, to the chip scale does not provide effective solutions. Moreover, any new technology must minimize meticulous sample preparation and handling steps, which limits the robustness of current technologies.
There has also been a growing need to develop microscale devices that can manipulate and transport relatively small volumes of fluids. These devices have applications in many areas of engineering, including propulsion and powered generation of micro-satellites, micro-air vehicles, inkjet printer heads, and bioanalytical instruments. See for example “PIV measurements of a microchannel flow” by C. D. Meinhart et al., Experiments in Fluids (1999) 414-419, the disclosure of which is incorporated herein by reference. When dealing with minute quantities of contaminants, for example, methods of separating or isolating the molecules to be diagnosed become important. Electrophoretic systems have been developed which aid in such techniques. Such systems separate molecules by their unique directed motions in an electric field.
In recent years, lasers have been put to use in molecular diagnostics. Robert Frankel et al. U.S. Pat. No. 5,637,458 (the disclosure of which is incorporated herein by reference) describes a system for biomolecular separation and detection of a molecular species that uses a solid state laser detector formed with a sample channel. The presence of a molecular species is indicated by a frequency shift in the laser's output which is detected by optical heterodyning the laser's output with the output of a reference laser. The interior of the sample channel can, optionally, be coated with a ligand for binding a molecular species of interest. The system involves rather complex preprocessing of the sample by electro-osmotic separation in channels that are lithographically formed in a two dimensional planar substrate and/or by a nanostructural molecular sieve formed of spaced apart posts defining narrow channels. Although an attempt at integrated system is provided by U.S. Pat. No. 5,637,458, it does not entirely provide a fully integrated optical chip device.
Also recently, highly coherent semiconductors, lasers and laser arrays have been developed primarily for telecommunications applications. See for example, C. E. Zah et al., IEEE Photon. Technol. Lett. Vol. 8 pp. 864-866, July 1996. In addition, widely tunable semiconductor lasers have been developed, in particular, sampled-grating distributed Bagg reflector (SGDBR) lasers. See, for example “Tunable Sampled-Grading DBR Lasers with Integrated Wavelength Monitors,” by B. Mason et al., IEEE Photonics Technology Letters, Vol. 10, No. 8 August 1998; 1085-1087 and “Ridge Waveguide Sampled Grating DBR Lasers with 22-nm Quasi-Continuous Tuning Range,” by B. Mason et al., IEEE Photonics Technology Letters, Vol. 10, No. 9 September 1998, 1211-1213. These widely tunable lasers are based on the use of two-multi-element mirrors as described in Coldren, U.S. Pat. No. 4,896,325. The foregoing also includes a Y-branch splitter with a detector in each branch for wavelength determination: Disclosures of the foregoing three publications and Coldren, U.S. Pat. No. 4,896,325 are incorporated herein by reference.